Quinoline derivatives



Patented Feb. 14, 1950 :QUINOLINiE DERIVATIVES Francis Henry .Swin'den Curd, Justus Kenneth handquistycliffor'd' GordonRztison, and Francis -LeslieRose, Blackley, Manchester, England, as-

I signors "to lmper'ial Chemical "Industries 'Iaimited, .a corporation'tof Great Britain .No Drawing. ApplicationJ uly 31-, 1945,.serial ,"No'. 608,086. In "Great Britain September "5,

4 7- Claims. (0!.260-286) This invention "relates to :the manufacture of new heterocyclic compounds, znamelynew quinoline and quinazolin'e: derivatives which: are useful as chemotherapeutic agents, and :particularly as parasiticidal agents, especially against the parasites that .cause mala-ria.

According to the invention wemake new quinoline and quinazoline derivatives which bear in the 2-:positionan .arylamino group C(asmore fully described below) and. iinithe 4-position :abasic group of the formula :NR' ---.A-NRRf .WhereiniR stands for hydrogen or .an alkyl orssimplyxsubstituted alkyl groupysuch as "an .a'lkoxyalkyl 'or dialkyl'aminoalkyl group, A stands for a linking group which is aliphatic or .alicyclic or aliphaticcarbocyclic and is devoid of .acidic sub'stituents but may .be substituted for examplabyhydrocarbon radicals, hydroxy ;or:alkoxy groups, or .dialkylaminoalkyl groupstandrwhere Ator fpart-o'f A is an aliphatic chain it may be interrupted by oxygen, nitrogen, or sulphur :atoma andNRR' is a strongly basic amino or substit.uted:amino group such as alkylamino or dialkyamino or piperidino or other strongly basic nitrogen-containing heterocyclic group, or an acylated primary or secondary amino group and which 'optionallylbear in the other nuclear positions one or more nonacidic substituents, for example,v alkyl, alkoxy, halogen or nitro groups, or fused-on carbocyclic rings (as, for example, in 6 zYi-benzoquinazoline .or '7 :B-benzoquinoline), by interaction of an appropriate 'arylami-ne with a quinoline or quinazo'line bearing in the 4-position the strongly basic group NR"-A-NRR' just referred to and in the '2- position a labile group such as a halogen atom or a hydrocarbon radical which is attached byan ether or thioether linkage, for. example, ,a chlorine or bromine atom, an aryloxyugroup or an .alkylmercapto group.

The reaction is conveniently brought aboutby heating the reagents togethenoptionally in presence of a solvent or diluent. A very convenient way of working is to use anaqueous medium with one molecular proportion each of the arylamine and the quinoline or quina zoline and one molecular proportion or a'slightexcess thereoverbf a mineral acid.

The arylam-ines to be used :as one class of start ing materials, and hence also the arylamino groups in the *z-positions of the final quinoline and quinazoline compounds maybe unsubstituted or substituted but they must be devoid of acidic substituents such as-su lphonic,- carboxylic or phenolic groups: Thustheyzmay bear one or more: non-acidic substituents such, for example; a's

, 2 halogen atoms, nitro groups, hydrocarbonradicals (which "them'selves may optionally bear simp'le 'substituents and which may be I attached to the arylamino group-directly or through an oxygen, nitrogen 'or 'sulp'hur atom or through 'asulphony1 or carbonyl group), cyan'o groups or' estei'ified carboxyl groups.

The 4-basically-substituted 2 halogeno quinolines may conveniently be made by interaction of "an 1 appropriate diamine with the' requ'isite 2 :4- dihydroxyquinolineas described'in 'cop'ending lapplication "of Curd/liaison, "and Rose, 'Se'ri'al No. 608;G85,-of even filin'g date herewith, 'now aban doned. lihe corresponding quiriazoline cempounds are'similaflyfmade from the diamine and the requisite 2:4-dicliloroquinazoline. "The-alternative starting materials, the quin'azolines or quinolines containing ether or thio'ether groups, can readily be made by interaction er the Z- halogeno derivatives with the appropriate hydroxy or mercapto compounds or with alkali metal derivatives of such oompounds.

' In many "of -thesenew 2 aryla1riirio4 siibsti tuted-quinolines or -quinazolines a substituent in the arylamino-group or in'the 'quin'o'lin'e or quin'af z'oline nucleus (and-more particularly in the b e'nzene ring thereof) is capable "of ready conversion into another suitable substituent. "Thusffor'example, a nitro group may be reduced'to an'ami'no group and this in f'turn may, if desired, beoon verted to a halogena'tomor a cyano group. Also in those cases "where th'esubstituen't in the l-pos'ition is the radical of an acylated di'amine the acyl radical can readily be removed, for example, by heatingwith a dilute acid.

Still a different mode of synthesis is disclosed in our copending application of even date,--ser ia1 No. 608,088, now Patent No. 2,488,379. -This mode of synthesis consistsof starting with aquiholine or quinazoline compound having an' aryIarnin radical, e. g. p-chloroph'enylami-no, in the "2-pos'i-' tion, and a labile atom or group, e. g. halogen, alkoxy, aryloxyi .or arylmercapto, the i-" position. This compound is then-reacted with=ah alkylene diamine compound of the formula acids such as-acetic', lactic, tartaric and lower alkanesulphonic acids (e. g. methanesulphonic acid) are water-soluble. The salts with acids of higher molecular weight such as methylene-bis- 2 B-hydroxynaphthoic acid and methylene-bissalicylic acid.v are more sparingly soluble in water.

The following examples illustrate, but do not limit, the invention. The parts are by weight.

Example 1 bonate and steam distilled to remove the excess of p-anisidine. The non-volatile oil remaining is dissolved in acetic acid and any undissolved impurities are removed b filtration. The cooled filtrate is made strongly alkaline with caustic soda solution and the base which is precipitated is extracted with ether. The ether solution is dried over anhydrous sodium sulphate and the ether is removed by distillation. The residual oil solidifies on standing, and is recrystallised from petroleum ether (B. P. 100-120 0.). It is 2-pmethoxyanilino 4-7-diethylaminopropylamino quinazoline. It forms colourless needles, M. P. 114-115 C.

In a similar manner the following compounds may be made: 2-anilino-4-y-diethylaminopropylaminoquinazoline (prisms, M. P. 112-114 C. from petrol), 2-p-toluidino-4-'y-diethylaminopropylaminoquinazoline (needles, M. P. 94 C., from petrol), 2-}3-naphthylamino-4-'ydiethylaminopropylaminoquinazoline (needles, M. P. 141- C. 'from aqueous ethanol) and 2p-chloroanilino- 4-'y-diethylaminopropylaminoquinazoline (prisms, M. P. 127 C. from petrol).

Example 2 4.65 parts of 2-chloro-4-fl-diethylaminoethylaminoquinazoline monohydrate (M. P. 80-81 C.) and 4.6 parts of p-thioanisidine are heated together in an oil bath at 130-140 C. for 3 hours. The clear glassy melt is diluted with 50 parts of water and the mixture is made alkaline to Brilliant Yellow paper and steam distilled to remove unchanged p-thioanisidine. The residual oil is dissolved up in acetic acid, and the solution is filtered and made strongly alkaline with caustic soda. The base which is precipitated is extracted with ether, the ether solution is dried over anhydrous sodium sulphate and the ether is dis-- tilled off. The residue is Z-p-methylmercaptoanilino-4-c diethylaminoethylaminoquinazoline. It forms asticky glass which on treatment with hydrochloric acid yields a crystalline dihydrochloride of M. P. 130l31 C.

In a similar manner, by employing fi-naphthylamine instead of p-thioanisidine, 2- (2-naphthylamino) 4-;8-diethylaminoethylaminoquin azoline (needles, M. P. 126 C. from aqueous ethanol) is obtained.

Example 3 5.6 parts of 2-chloro-4- 8-diethylaminoethy1- aminoquinazoline monohydrate, 5.1 parts of pchloroaniline and 10 parts of glacial acetic acid are boiled under reflux for 2 hours. The mixture is poured into 100 parts of water and the solution is filtered from undissolved material (p-chloroacetanilide). The filtrate is treated with half the amount of caustic soda required to make it alkaline to Brilliant Yellow paper (determined by separate test on an aliquot portion of the solution) and any unchanged p-chloroaniline ls removed by extraction with ether. The aqueous solution is made strongly alkaline with caustic soda, and the base which, is liberated is extracted with ether. The other solution is extracted twice with 5% aqueous acetic acid parts and 20 parts) and the acid extracts are combined and stirred with decolourising carbon (1 part), filtered and treated with 30 parts of concentrated hydrochloric acid. After a short time the dihydrochloride of 2-p-chloroanilino-4-fi diethylaminoethylaminoquinazoline separates out as a felted mass of white needls, M. P. 254-255 C. The free base, readily obtained by adding an eX- cess of caustic soda to the hydrochloride, crystallises from petrol in small white prisms, M. P. 111-112 C.

Instead of the acetic acid, ,B-ethoxyethanol or phenol may be employed as a solvent.

In a similar manner, by employing 2-chloro- 4-,8-dimethylaminoethylaminoquinazoline (M. P. 96-98 C.), 2-chloro-4-v-dimethylaminopropylaminoquinazoline (M. P. 74 C.), 2-chloro-4-v-nbutylaminopropylaminoquinazoline (sinters at 94 C., M. P. indefinite), '2-ch1oro4-6-diethylaminobutylaminoquinazoline' (monohydrate, M. P. 71 C.) and 2-chloro-4-7-piperidinopropyl aminoquinazoline (M. P. 148C.) instead of the 2 chloro 4 {3 diethylaminoethylaminoquinazoline there are obtained, respectively, 2-pchloroanilino-4 B dimethylaminoethylaminoquinazoline (dihydrochloride, M. P. 267-268 C.), z-p-chloroanilino 4 'y dimethylaminopropylaminoquinazoline (dihydrochloride, M. P. 256- 258 C.), 2-p-chloroanilino-4v-n-butylaminopropylaminoquinazoline (dihydrochloride, M. P. 254256 C.), 2-p-chloroanilino-4 6 diethylaminobutylaminoquinazoline (dihydrochloride, M. P. 260-262 C.) and 2-p-chloroanilino-4-q piperidinopropylaminoquinazoline (dihydrochloride, M; P. 285-286 C.)

Eccample 4 A mixture of 8.1 parts of 4-v-diethylaminopropylamino-2-chloroquinoline, 10.65 parts of pchloroaniline and 0.1 part of potassium iodide is heated with stirring in an oil bath at 200 C. for 6'hours. After cooling, the reaction mixture is dissolved in dilute hydrochloric acid, the solution is basified with caustic soda and the product which separates out is extracted with chloroform. The chloroform is distilled off and to the residue 100 parts of 5% acetic acid are added and the mixture shaken with ether. The dilute acetic acid solution is separated, basified with caustic soda and shaken with chloroform. The chloroform extract is dried with anhydrous potassium carbonate, and the chloroform is distilled off. The remaining oil solidifies on cooling, and after crystallisation from benzene gives crystals of 4- 'y-diethylaminopropylamino 2 p-chloroanilinoquinoline melting at 154-156 C.

E :rample 5 water and filtered, and the solid residue is ex-.

tracted repeatedly with 5% aqueous acetic acid (in all 500 parts).

added whereupon 2,-(6 bromo 2' naphthyl- The acid extracts are com-- bined and concentrated hydrochloric acid is;

amino) 4 p diethylaminoethylaminoquinazoline dihydrochloride is precipitated. This is purifled by recrystallisation from water and'then has M. P. 284-285 C.

In a similar manner, by employing 4.2 parts of 4:8-dichloro-2-naphthylamine instead of the 4.5 parts of 6-bromo-2-naphthylamine, 2-(4':8'- dichloro 2 naphthylamino) 4 p diethylaminoethylam'inoquinazoline dihydrochloride, M. P. 284 C. is obtained.

Example 6 6.3 parts of 2:7-dichloro 4 ,6 diethylaminoethylam'inoquinazoline (dihydrate, M. P. 84-85 C.), 5.1 parts of p-chloroaniline and parts of glacial acetic acid are boiled under reflux for 2 hours. The mixture is cooled, diluted with 80 parts of water, filtered from p-chloroacetanilide, and made just alkaline to Clayton Yellow paper with sodium hydroxide solution. The mixture is then steam distilled, whereby unchanged p-chloroaniline is removed. The quinazoline (as free base) separates out in the distillation vessel and is filtered off when cold and dissolved in 100 parts of hot 5% aqueous acetic acid. The solution is filtered, and 50 parts of concentrated hydrochloric acid are added whereupon 7-chloro-2- p-chloroanilino 4 ,s-diethylaminoethylaminoquinazoline dihydrochloride is precipitated in the form of small white needles, M. P. 280"-283 C. The free base readily obtained by treatment of the hydrochloride with an excess of caustic soda crystallises from petrol as yellowish white nodular masses, M. P. 121-122 C.

In a similar manner, by employing, 6.3 parts of I 2 :6 dichloro-4-p-diethylaminoethylaminoquinbenzoquinazoline dihydrochloride separates as a yellow solid and is purified by crystallisation from 150 parts of hot water with the addition of 20 parts of concentrated hydrochloric acid to assist the separation of the salt in a filterable form. It is a sulphur yellow powder, M. P. 286-28'7 C.

Example 8 6.77 parts of 2-chloro-4-p-diethylaminoethylamino-6:7-dimethoxyquinazoline (M. P. 116- 117 C.) 5.1 parts of p-chloroaniline and 10 parts of glacial acetic acid are boiled under reflux for 3 hours. The mixture is cooled, diluted with 80 parts of water at 6070 C. and filtered from .pchloroacetanilide, the latter being washed with parts of water. The filtrate and washings are combined, made alkaline by the addition of so dium carbonate and steam distilled to remove pchloroaniline. The oil which remains in the distillation vessel is separated from the aqueous liquor and dissolved in 50 parts of 5% aqueous acetic acid and the solution is clarified with decolourising charcoal. 30 parts of concentrated hydrochloric acid are then added, whereby the dihydrochloride of 2-p-chloroanilino 4 -p diethylaminoethylamino 6:7 dimethoxyquinazoline is precipitated. After recrystallisation from water this melts at 255-256 C.

Example 9 6 parts of 2-chloro 4- ,3 diethylaminoethylaminoquinazoline monohydrate, 3.3 parts of p-' chloroaniline hydrochloride, 20 parts of water M. P. 264 C.), 2-p-chloroanilino-4-,3-diethyl- Eaample 7 '1 parts of 2-chloro 4 p diethylaminoethyL amino-6z'l-benzoquinazoline (M. P. 150 C.), 5.1 parts of p-chloroaniline and 10 parts of glacial acetic acid are boiled under reflux for 2 hours. The mixture is diluted with 80 parts of water, heated to 70 C. and filtered. The residue is extracted twice with parts of water at C. The combined filtrates, which set to a gel on cooling,

are heated until clear, and 30 parts of concen-i trated hydrochloric acid are added. 2-p-chloroanilino" 4 p diethylaminoethylamino 6:1--

and 0.1 part of concentrated hydrochloric acid are stirred and heated together under reflux for 1 hour. The solution is then cooled, whereupon 2 p-chloroanilino-4-p-diethylaminoethylaminoquinazoline dihydrochloride separates out. It is filtered off and recrystallised from water; it then has M. P. 254-256 C.

By working in a similar manner, but using 6.1 parts of 2-chloro-4 Y piperidinopropylaminoquinazoline or 5 parts of 2-chloro-4-p-dimethylaminoethylaminoquinazoline or 6.9 parts of 2-.

.- chloro 4-,8-diethylaminoethylamino 5 methoxyquinazoline dihydrate instead of the 2-chloro- 4 p diethylaminoethylaminoquinazoline there are obtained, respectively, 2-p-chloroanilino-4-ypiperidinopropylaminoquinazoline dihydrochloride (M. P. 285-286 C.), 2-p-chloroanilino-4-pdimethylaminoethylaminoquinazoline chloride (M. P. 267-268 C.) or 2-p-ohloroanilino-4-p-diethylaminoethylamino 5 methoxyquinazoline dihydrochloride (M. P. 187-188 0.). Likewise by condensing 6 parts of 2chloro-4-p diethylaminoethylaminoquinazoline monohydrate with 3.5 parts of p-nitroaniline hydrochloride under these same conditions there is obtained 2-pnitroanilino 4 18-diethylaminoethylaminoquinazoline dihydrochloride of M. P. 286287 C.

Example 10 6.5 parts of 2-chloro-6-nitro-4-s-diethylaminoethylaminoquinazoline, 5.1 parts of p-chloroaniline and 10 parts of glacial acetic acid are reparts of concentrated hydrochloric acid are add-- ed, whereupon 2-p-ohloroanilino-S-nitro-4- 8-diethylaminoethylaminoquinazoline ride is precipitated.

' dihydrochlo-v It is filtered 011. and re-u crystallised from water; it then has. M. P. 266 C11.

The free baseis readily obtained byadding caustic soda to an aqueous solution of the dihydrochloride; after crystallisation from ethanol or B- ethoxyethanol it has M. P. 2G0-201 C. It can be readily reduced with hydrogen at ordinary pressure and a Raney nickel'catalyst in methanol to the corresponding 6-amino compound. 2-pchloroanilino 6 amino-443-diethylaminoethylamino-quinazoline trihydrochloride crystallises from water as a pentahydrate with M. P. 180 C., solidifying again on further heating and remelting at 286 C.

Example 11 17.7 parts of 2-chloro--B-acetylaminoethylaminoquinazoline (M. P. 206207 C.) 9 parts of p-chloroaniline and 30 parts of glacial acetic acid are refluxed together for 3 hours. The mixture is diluted with 300 parts of hot water and filtered. 100 parts of saturated sodium chloride solution and 30 parts of concentrated hydrochloric acid are added to the filtrate, whereupon 2-p-ch1oroanilino 4 e acetylaminoethylaminoquinazoline hydrochloride is precipitated in the form of white platelets, M. P. 278280 C. The residue which remained undissolved by the aqueous acetic acid is converted to the free base by trituratin with 20 parts of cold ethanol and 7 parts of 30% sodium hydroxide solution and 100 parts of Water are added whereupon 2 p-chloroanilinol-fi-acetylaminoethylarninoquinazoline separates out. After crystallisation .from ethanol it has M. P. 183-184 C.

8.5 parts of 2-p-chloroanilino-4-l9-acetylaminoethylaminoquinazoline, 30 parts of concentrated hydrochloric acid, 15 parts of water and 50 parts of ethanol are refluxed together ,for 3 hours, and the mixture is thenpoured into .300 parts of 5% caustic soda solution. The base which is precipitated is purified by crystallisation from petroleum ether, or by conversion to its dihydrochloride and crystallisation from water. 2-p-chloroanilino-4- B-aminoethylaminoquinazoline crystallises from petroleum ether in fine needles of M. P. 132 C. The dihydrochloride is a white solid, M. P. 314- 316 C.

Example 12 6 parts of 2-c'hloro-4-fi-diethylaminoethylmethylaminoquinazoline trihydrate, 5.1 parts of p-chloroaniline and 10 parts of glacial acetic acid are refluxed together for 3 hours. The reaction mixture is diluted with 100 parts of boiling water and filtered. The residue is Washed with 50 parts of boiling water and the extract is added to the filtrate. This solution is then made alkaline with caustic soda whereupon a mixture of the base and unchanged p-chloroaniline separates out. The while mixture is steam distilled to remove the p-chloroaniline. vessel is then extracted with ether. The ether is evaporated off and the residue is crystallised from ligroin or from aqueous ethanol. Z-p-chloroanilino 4 methyl-5-diethylaminoethylaminoquinazoline dihydrate is thus obtained as colourless crystals, M. P. 76 C.

Example 13 6 parts of 2-chloro--fi-diethylaminoethyl-- aminoquinazoli'ne monohydrate and 6.5 parts of N-ethylaniline are heated together at 140150 C. for 2 hours. The reaction mixture is diluted with water and made alkaline by the addition of sodium carbonate. A mixture of the base with unchanged ethylaniline separates out. The whole mixture is steam :distilled to remove the ethyl-- The residue in the distillation v aniline. The residue in the distillation vessel .is then acidified with acetic acid .and filtered and caustic soda solution in excess is added to the filtrate whereupon 2-N-ethylanilino-4-B-diethylaminoethylaminoquinazoline is precipitated as a crystalline solid. After recrystallisation from aqueous ethanol it has M. 1?. C.

Example 14 A mixture of 5.15 parts of 2-chloro-4- -diethylaminopropylaminoquinoline, 2.25 parts of pchloroaniline, 2 parts of concentrated hydrochloric acid, 20 parts of Water and 5 parts of ethanol, is boiled under reflux for48 hours. After cooling, sodium acetate solution is added until furtheraddit-ion no longer produces a precipitate. This precipitate is unchanged p-chloroaniline; it is extracted with ether and discarded. The remaining aqueous solution is made alkaline with caustic soda, whereupon 2-.p-chloroanilino-4- diethylaminopropylaminoquin'oline is precipitated and is filtered off. After crystallisation from benzene it has M. P. 155 156 C.

Example 15 A mixture of 9.65 parts of 2-chloro-4-Y-diethylaminopropylamino-3-methylquinoline, 12.1 parts of .p-chloroaniline and 0.1 part of potassium iodine is heated at 200 C. for 12 hours. After cooling, the reaction mixture is dissolved in dilute hydrochloric acid, the solution is made alkaline with caustic soda and the precipitate which is formed is extracted with chloroform. The chloroform is distilled off, par-ts of 5% acetic acid are added to the residue and the mixture is shaken with ether. The ether layer is discarded and the aqueous acetic acid solution made alkaline with caustic soda and extracted with chloroform. The chloroform extract is dried over anhydrous potassium carbonate and the chloroform is distilled ofi. The residual oil consists of 2-p-chloroanilinoldiethylamino-propylamino 3 methylquinoline. It forms a diperchlorate which crystallises in colourless needles from ethanol and melts at 2l6. 218 C.

Example 16 A mixture of 8 parts of 2-chloro-4-fi-diethylaminoethylaminoquinoline, 10 parts of p-chloroe aniline and 0.1 part of potassium iodide is heated with stirring at 200 C. for 10 hours. After cooling, the mixture is dissolved in dilute hydrochloric acid, the solution is made alkaline with caustic soda and the precipitate which is formed is ex tracted with chloroform. The chloroform is distilled off. 100 parts of 5% acetic acid are added to the residue and the mixture is shaken with ether. The ether layer is discarded. The aqueous acetic acid solution is made alkaline with caustic soda and the base which is precipitated is extracted with chloroform. The chloroform solution is dried over anhydrous potassium carbonate and the chloroform is distilled ofi. The remaining oil consists of 2 p chloroanilino-4=-,6-diethylaminoethylaminoquinoline. It forms dihydrochloride, M..P. 169"--1'71 C.

Example .1 7

8.96 parts of 2:'Y-dichloro-4-7ediethylaminopropylaminoquinoline, 10.6 parts of p-chloroaniline and 01 part of potassium iodide are heated at200 C. with stirring for 8 hours. After cooling the reaction mixture is diluted with water and sufiicient causticsoda :is added to render the 75 mixture strongly alkaline. Unchanged'p-chloroether it has M. P. 14414=5 C.

Whereas the above description and examples illustrate many widely varied embodiments of the invention, it will be apparent to one skilled in the art that many other embodiments and variations may be devised without departing from the spirit and scope thereof and accordingly it is to be understood that the invention is not in any way limited except as defined in the following claims.

In the claims below,.the expression N-radical when referring to a nitrogenous base shall be understood as referring to the radical obtained by removing one of the hydrogen atoms which are (or the only hydrogen atom which is) attached to the nitrogen atom of the specified base. The expression devoid of acidic substituents as used in the claims shall be construed as referring to freedom from radicals which are commonly recognized as ionizable, salt-forming acid radicals, as typified by the carboxy, sulfonic acid and phenolic OH radicals.

We claim:

1. A compound selected from the group consisting of the salts and free-base form of 2-arylamino-4-substituted quinolines, which in the form of free base have the formula wherein Z stands for an aryl radicalof the benzene series being devoid of acidic substituents, R" designates a member of the group consisting of hydrogen and lower alkyl, A stands for an aliphatic radical devoid of acidic substituents, while the radical Q represents the N-radical of a nitrogenous base selected from the group consisting of lower monoalkyl amines, lower dialkyl amines and saturated heterocyclic amines.

2. As new compounds, 2-arylamino-4-substituted quinolines having the general formula:

wherein A is a lower alkylene radical; R and R1 are lower alkyl radicals, and X is a halogen radica 3. As new compounds, 2-arylamino-4-substituted quinolines having the general formula:

. wag;

NH-A-NHR wherein A is a lower alkylene radical; R is a lower alkyl radical, and X is a halogen radical.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date 2,233,970 Andersag et al. Mar. 4, 1941 FOREIGN PATENTS Number Country Date 134,279 Switzerland Oct. 1, 1929 669,806 Germany Jan. 4, 1939 681,980 Germany Oct. 5, 1939 OTHER REFERENCES Niementowski: Berichte 40, 428544294, 1907.

Buchmann et al.: J. Am. Chem. Soc, 64, 1357- 1360 (June 1942).

Wiselogle: Survey of Antimalarial Drugs 1941- 1945" (J. W. Edwards, Ann Arbor,'Mich., 1946) vol. II, p. 1152. 

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF THE SALTS AND FREE-BASE FORM OF 2-ARYLAMINO-4-SUBSTITUTED QUINOLINES, WHICH IN THE FORM OF FREE BASE HAVE THE FORMULA 